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CN1585894B - Cryostorage method and device - Google Patents

Cryostorage method and device Download PDF

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Publication number
CN1585894B
CN1585894B CN018201458A CN01820145A CN1585894B CN 1585894 B CN1585894 B CN 1585894B CN 018201458 A CN018201458 A CN 018201458A CN 01820145 A CN01820145 A CN 01820145A CN 1585894 B CN1585894 B CN 1585894B
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China
Prior art keywords
sample
matrix
sample data
cold
carrier
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CN1585894A (en
Inventor
京特·富尔
罗尔夫·阿赫多恩
海科·齐默尔曼
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Fraunhofer Gesellschaft zur Forderung der Angewandten Forschung eV
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Fraunhofer Gesellschaft zur Forderung der Angewandten Forschung eV
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Priority claimed from DE2000160889 external-priority patent/DE10060889A1/en
Priority claimed from DE2001144925 external-priority patent/DE10144925A1/en
Application filed by Fraunhofer Gesellschaft zur Forderung der Angewandten Forschung eV filed Critical Fraunhofer Gesellschaft zur Forderung der Angewandten Forschung eV
Publication of CN1585894A publication Critical patent/CN1585894A/en
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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/508—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above
    • B01L3/5085—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above for multiple samples, e.g. microtitration plates
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N1/00—Preservation of bodies of humans or animals, or parts thereof
    • A01N1/02—Preservation of living parts
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N1/00—Preservation of bodies of humans or animals, or parts thereof
    • A01N1/02—Preservation of living parts
    • A01N1/0236—Mechanical aspects
    • A01N1/0263—Non-refrigerated containers specially adapted for transporting or storing living parts whilst preserving, e.g. cool boxes, blood bags or "straws" for cryopreservation
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N1/00—Preservation of bodies of humans or animals, or parts thereof
    • A01N1/02—Preservation of living parts
    • A01N1/0236—Mechanical aspects
    • A01N1/0263—Non-refrigerated containers specially adapted for transporting or storing living parts whilst preserving, e.g. cool boxes, blood bags or "straws" for cryopreservation
    • A01N1/0268—Carriers for immersion in cryogenic fluid, both for slow-freezing and vitrification, e.g. open or closed "straws" for embryos, oocytes or semen
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L7/00—Heating or cooling apparatus; Heat insulating devices
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N1/00—Sampling; Preparing specimens for investigation
    • G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
    • G01N1/42—Low-temperature sample treatment, e.g. cryofixation

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Hematology (AREA)
  • Dentistry (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Environmental Sciences (AREA)
  • Clinical Laboratory Science (AREA)
  • Mechanical Engineering (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Analytical Chemistry (AREA)
  • Physics & Mathematics (AREA)
  • Biochemistry (AREA)
  • General Physics & Mathematics (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • Sampling And Sample Adjustment (AREA)
  • Automatic Analysis And Handling Materials Therefor (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Investigating Or Analysing Biological Materials (AREA)

Abstract

With a method for cryo-preservation, at least one specimen is arranged on a storage substrate and specimen data, which are characteristic for features of the specimen, are stored at specific positions. Also, a storage substrate for cryo-preservation with such a method is described.

Description

The method and apparatus of cold storage
The present invention relates to a kind of method that is used for the cold storage of sample, in particular under refrigeration or thawed state to manufacturing, storage and the processing of biological sample, for example be used for the cold preserving method of biological cell.The invention still further relates to the method that reads and writes data.The invention still further relates to the device that is used for the cold storage of sample, in particular for the biological sample storage matrix of cell or cellular component for example; And be used for the device that reads and writes data in storage medium and freezer system.The invention still further relates to the use of the biological sample of refrigeration.
Refrigeration is the known method that is used for preserving (particularly) biology or medical material.These materials for example comprise tissue and organ, body fluid or independent cell or cellular component.Refrigeration is carried out in container or on the matrix according to prior defined procedure, and the shape of this container or matrix and material or sample adapt.The container that is used to refrigerate is known for example to be used for tissue and organ (seeing DE-OS1992231, EP-A0853238, DE-OS19725768, DE-OS19905163), to be used for blood constitutent (for example seeing DE-OS19826350) and to be used for cell or the cold sample of droplet-shaped (for example seeing U.S. Patent No. 5275016, EP-B0475409, DE-OS19921236, EP-B0804073).
For the refrigeration of biological sample, what usually be concerned about is recognition capability to sample.Cold sample must be discerned their source and feature very definitely under the situation that does not need to thaw.For macroscopic sample, this is not a problem, because organ or blood vessel can provide sign (inscription).Cold sample positions according to the stocking system of corresponding freezer.
For the less freezing sample that becomes freezing hanging drop, cell, cell aggregate or cellular component form, the identification of cold sample becomes problem.Compare with sign, cold sample is less, may ignore.Usually, will refrigerate a large amount of tiny samplers.By sign less cold sample is stored and identification is unpractical.In addition, by based on the common store method (for example seeing EP-B0475409) that cell suspending liquid is sprayed onto on the cold surface, may obtain the refrigeration cell sample of mixed and disorderly state.A large amount of independent samples is stored with not indicating jointly and.
For the storage method described in EP-B0804073 and the DE-OS19921236, on cold matrix, even minimum sample also can have position and carry out particular procedure.For example, can carry out sample deposition by utilizing the droplet emitter, this device is controlled according to the intended target coordinate.Sample arrangement also can be carried out the particular measurement of sample characteristics of for example and the identification of sample on this substrate location on the substrate location of determining.This matrix can provide mark, so that determine the position of sample on matrix.For example, in DE-OS19921236, for the rectangular deposition of the cold sample that is in line and is listed as, matrix can have the indication of row and straight line.This labeling method is represented in Figure 27 (prior art).
Cold matrix general labeling according to Figure 27 has following shortcoming.Although can discern sample, but, only about the information of position.But, the limited information capacity of matrix mark is a problem, because except sample identification, also should obtain other data, for example the account of the history of this sample or measurement result.These data can be stored in the database of operation repetitive.But, the separate operation of freezer and database has very big danger for the reliability of each sample characteristics of for example.Especially when being used for medical-therapeutic treatment of human body, this danger is very crucial, because particular error may make cold sample further not use.In addition, the shortcoming of matrix mark is to have only in conjunction with cold matrix just to carry out sample identification.When taking out sample, for example described in the DE-OS19921236, with after cold matrix is separated, sample identification can only be undertaken by under thawed state special characteristic being carried out expensive measurement.
By a kind of as can be known sample carrier that is used for the micro-analysis of a large amount of samples of DE-OS19752085.This common sample carrier is formed by the matrix with a large amount of sample reception space, shown in the schematic plan view among Figure 28 (prior art).This matrix for example is plate storage medium (for example CD) shape.Between the access opening at matrix center and corresponding rectangular sample reception space, be formed with annular region.Form these annular regions as can be known by DE-OS19752085, be used for the stored sample data.The shortcoming of this common sample carrier is that it can only be used to receive fluid sample, can not be used for refrigeration.In addition, sample data is stored in also has in the inner loop and the identical shortcoming of above-mentioned matrix mark.But, when storing more multidata, can not interrelate with each sample under the wrong situation not having.
Except the described shortcoming of ordinary skill, the minority development purposes for refrigeration also has following situation, especially aspect cellular biological technique.When in the liquid cooled stage (for example nitrogen), carrying out biological sample direct freezing, the danger of pollution is arranged.At cooling stage, virus may pass on the sample.For fear of this danger, must avoid contacting maybe and must sealing covering this sample with liquid phase.Up to now, this still can not actually realize.
By the sample carrier of known for example article carrier of laboratory technique or microtitre plate form, they are equipped with data storage media.These common sample carriers are not suitable for refrigeration.At first, they only are suitable in room temperature or are being higher than under the cryogenic temperature of freezing point of water using.Purposes at low temperatures can not realize.The second, the common sample carrier is as the matrix that is used for sample.The processing of sample, operation or cultivation are all carried out on this matrix.But, in order to store under preservation state, common sample carrier is also improper.At this moment, adopted the container that is used to refrigerate, as mentioned above.At last, the common sample carrier is not suitable for effective sample storage and handles.In fact, they must manually transport, and therefore can not carry out highdensity storage.
The purpose of this invention is to provide a kind of improved cold preserving method, can overcome the shortcoming of ordinary skill, and this method can be extensive use of, especially be suitable for automatic preservation and storage by this method.Especially, the new method that is used to refrigerate can be held sample data with greater amount and the mode with higher data reliability (reliability of getting in touch between raising sample data and the definite sample just).The present invention can also make data link to each other with each cold sample very clearly.An also purpose of the present invention provides a kind of device that is used to realize above-mentioned improvement cold preserving method.
This purpose realizes by method or device with claim 1,12, feature of 21 and 22.The preferred embodiments of the present invention and purposes provide in the dependent claims.
Basic thought of the present invention be with at least one sample arrangement on matrix, and on matrix the stored sample data, this sample data is represented the feature of cold sample.Preferably, sample data is stored in ad-hoc location in the sample data storage medium in the storage position of respective sample.By sample and sample data being stored in the public or next-door neighbour or the adjoining position of matrix, can obtain a series of advantage.Sample data can clearly be got in touch with respective sample by their storage location.In sample relation, can not make a mistake.When taking out sample, corresponding data is read simultaneously or is taken out from matrix with storage medium, therefore, after taking out sample and further handling, can guarantee sample identification and with the getting in touch of sample data.Each sample can be taken out under suitable temperature, especially under freezing state, take out.
Improvement of the present invention is, at first, can provide method and appropriate device, and this method and apparatus can make biological sample (for example be lower than-50 ℃) for a long time at a lower temperature in (several months and several years) directly to optimize storage.By the present invention,, can obtain the new use field under working temperature, and this can not realize before the present invention for the use of data-carrier store.
According to purposes, sample is deposited with data storing and can at room temperature be carried out, and freezing subsequently to required storage temperature, perhaps also can carry out under freezing state.The inventor surprisingly finds, can make data in known stored medium (for example optical memory, magnetic store, electromagnetic storage, FLASH storer), write and read under the storage temperature of the freezing point that is lower than water, perhaps write and read at the specific storage medium that is used for refrigerating purpose.The sample data group can reliably be read in all stages that refrigeration is handled.The readability (except data write) of data-carrier store under such low temperature is the advantage that the inventor knows, it has represented the availability widely of the present invention's refrigeration.
The present invention is particularly advantageous to be, a large amount of samples are stored on the public storage matrix, and a plurality of sample data groups have the specific storage position simultaneously.Store matrix simultaneously as having the cold matrix of sample carrier and as data carrier, this sample carrier is used for receiving, keep and discharging cold sample, and this data carrier with mass data storing with the corresponding substrate location in respective sample position, as storage medium known in computer technology.The sample part applies at the sample carrier of cold matrix, and isolates (for example, as the cell suspending liquid drop) as the cell suspending liquid volume.Each sample carrier links to each other with the sample data storage medium, and conjoint data is stored in the sample data storage medium.Sample and sample data store simultaneously, and like this, it can keep stable for a long time, and guarantee to prevent to mix.Refrigeration of the present invention is called " cold storage ", because store similar with electronic data.
According to a preferred embodiment of the invention, cold storage is carried out storing on the matrix by at least one cold storage unit.Each cold storage unit comprises sample carrier and sample data storer, and they form global facility each other, and this global facility is reversible or irreversibly remove from matrix.Sample carrier and data-carrier store are formed with fixed connecting piece, and this fixed connecting piece is removably mounted on the storage matrix that is used for cold storage.In order to take off sample from storing matrix, whole cold storage unit takes off from storing matrix.Theme of the present invention also has cold storage unit, and this cold storage unit comprises: sample carrier is used to receive cold sample; The sample data storer is used to store the respective sample data.According to a preferred embodiment of the invention, store matrix and formed by matrix, this matrix is preferred for flat pattern, and a plurality of cold storage units are arranged.According to purposes, this storage matrix can have predetermined bidimensional or 3 dimensional coil geometry.According to a preferred embodiment of the invention, the matrix that stores matrix has light storage disks (CD-ROM) shape, and wherein combination has cold storage unit, perhaps is at least one wiring board shape, and cold storage unit is arranged on this wiring board as circuit (chip).
Theme of the present invention also has a kind of method that is used to operate the freezer of a plurality of storage matrix.Store on the matrix at least one, store a plurality of samples, these samples for example belong to organism (test theme).This sample for example comprises the specific cells (for example stem cell, histocyte) of at least one test theme.At first, the storage of sample is carried out with the specific sample data, especially stores with the identification data of identification data, the storage time point of sample type and test theme and at the identification data of the measurement of storage time point.When freezer was worked, sample took out with the respective sample data, for use in measurement purpose, diagnostic purpose or methods of treatment, and/or further replenished sample or sample data.Sample data comprises basic all features and the parameter of sample and sample donor (donor), when needing, can be the additional data that is used for storing store information on the matrix.For example, the sample data storer of the present invention's use has the storage volume of at least 4 megabyte.
By the following preferred feature of the cold storage of the present invention, can overcome the shortcoming of common plane or three dimensional matrix.Sample (for example freezing cell suspending liquid) can be put approaching at any time.This also can carry out under cryogenic conditions.The minimal sample volume can be arranged in definite substrate location, and their characteristic dimension is in the scope of mm or littler, and but, preferably, common amount is 10 3μ m 3(10 * 10 * 10 μ m 3) to several 10nm 3Sample for example can comprise one or more cells (10 5To 10 6), cell component, associated biomolecule material (for example membrane vesicle, DNA material, big molecule) and/or cell adhesion body (cell bond).Sample can arrange to high-density that the efficient of cold storage improves.
Sample can selectively take out storing under the cryogenic of matrix, simultaneously can all the other samples of overslaugh freezing.In order to go back raw sample and sense data, do not need to make whole storage matrix to thaw.
Sample data can be read and write automatically by computing machine.The contact of sample data storer and sample carrier is unique.Sample stores, and their assurances can wrong identification like this.Getting in touch and being kept with getting in touch all of matrix of storage of the sample that takes out and sample data like this, can be summarized the history of sample.This has special advantage for medical application of the present invention.
Preferably, but the compatible plastic material formation of cold storage unit utilization low temperature of the present invention, and this plastic material forms sample carrier on the one hand, and the sample data storer is embedded.Plastic material can bear the temperature variation of repetition under the situation that does not have variation and damage.Preferably, the water-intake capacity of used plastic material is less than 1% of deadweight, especially less than 0.1% of deadweight.For example, cold storage unit of the present invention is based on polycarbamate, teflon or tygon.The advantage of storage matrix of the present invention is to have very high mechanical stability and very long serviceable life.Cold storage of the present invention at first can guarantee to store Biosample and surpass decades.Freezer can be in the whole longer life of donor (test theme) reliably working, for example in people's whole life.Storing matrix has simple relatively structure, and this makes to use in a large number in freezer and stores matrix.
The present invention is also very favourable aspect described pollution dangerous.Storage matrix of the present invention can have the series of features of introducing below, by these features, can prevent that the liquid freezing medium from contacting with sample.Under freezing state, avoid viral pollution.Also have, water or other material can not condense on sample.
An also significant advantage of storage matrix of the present invention is can be near stored sample under refrigeration identical with analytical approach (for example optical measurement, micro-analysis) with measurement and readable data simultaneously or thawed state.Data in the sample data storer are also by a plurality of freezing or thaw to handle and keep.
Cold storage is undertaken by the condition of storage of selecting according to purposes.The circular order that the temperature of cold storage and temperature reduce and increase can be selected according to preserving object and material.Storage temperature preferably is lower than the freezing point of water under normal pressure in being lower than the zone of room temperature, preferably be lower than under-80 ℃ the temperature to use for a long time.Preferably, refrigerated storage temperature is regulated by the steam of liquid freezing medium (nitrogen) or this refrigerant.
Advantage of the present invention be can cold storage minimum volume sample.This can accelerate temperature variation, preservation condition can be reproduced, and carries out operation, processing or the measurement of single sample.
Introduce other advantage of the present invention and feature below with reference to the accompanying drawings.In the accompanying drawing:
Fig. 1 is the schematic sectional view that stores the part of matrix according to the present invention of first embodiment of the invention;
Fig. 2 is sample is taken out in expression from the storage matrix of Fig. 1 a synoptic diagram;
Fig. 3 to 7 is storing the various forms of samples on the matrix and the schematic plan view of memory structure;
Fig. 8 is the schematic sectional view according to the part of the storage matrix of second embodiment of the invention;
Fig. 9 is the synoptic diagram of the various geometries of cold storage unit;
Figure 10 is the schematic sectional view according to the part of the storage matrix of third embodiment of the invention;
Figure 11 is the view that stores the specific cold storage unit that takes out the matrix from the present invention of fourth embodiment of the invention;
Figure 12 is the synoptic diagram of the membranaceous lid on storage matrix of the present invention;
Figure 13 is the schematic sectional view according to the part of the storage matrix of fifth embodiment of the invention;
Figure 14 is the perspective illustration according to the storage matrix of sixth embodiment of the invention;
Figure 15 is the perspective illustration of cold storage unit of the storage matrix of Figure 14;
Figure 16 is the perspective illustration of version of the cold storage unit of Figure 15;
Figure 17 to 20 is perspective illustrations of going back the cold storage unit of the present invention of an embodiment according to the present invention;
Figure 21 and 22 is synoptic diagram of the taking-up of the loading of sample carrier and sample;
Figure 23 to 26 is according to the present invention and the present invention of an embodiment stores the perspective illustration of matrix; And
Figure 27 and 28 is planimetric maps (prior art) of common sample carrier.
According to the present invention, in the sample carrier of at least one sample arrangement on matrix, and on matrix, store sample data, this sample data is represented the feature of cold sample.Sample data is stored in the ad-hoc location of sample data storer, preferably at the storage location of respective sample.The sample data storer that is used to receive the sample carrier of cold sample and is used to store corresponding storage data is called " cold storage unit " together.Storage matrix optimization of the present invention is to form base body, and this base body is preferred for flat pattern, has a plurality of cold storage units.
First embodiment for as shown in Figure 1 storage matrix 100 of the present invention provides matrix 110, a plurality of cold storage units 120 of these matrix 110 supportings.Matrix 110 (representing with cut-away) has common size, but optical read/write storage disks (below be called: CD, diameter be about 12cm for example) for example.In order to receive cold storage unit 120, this matrix 110 has access portal 111, and cold storage unit places this access opening 111 with the press fit form.Be arranged in film shape storage medium 112 on one side of matrix 110.Storage medium 112 is data Layers, and for example its type is known common CD type, and is suitable for reading and writing data.Preferably, this storage medium 112 is designed for light and writes (" firing (burning) ") and sense data.But, it also can be magnetic storage medium or topological structure (topographic) storage medium.When needing, on storage medium 112, provide the protective seam (not shown).
Storage medium 112 comprises: be positioned at the layer region on the matrix 100, this layer region is as pedestal storer 113; And the zone that links to each other with cold storage unit 120, this zone is as sample data storer 122.Pedestal storer 113 and sample data storer 122 at first form the closed layer of storage medium 112, and when needs, this closed layer is destroyed after taking out sample.Pedestal storer 113 preferably is equipped with the matrix data, and these matrix data for example relate to the identification of the structure type and the matrix of cold storage unit.Sample data storer 122 is equipped with sample data (face as follows).
Cold storage unit 120 comprises sample carrier 121 and sample data storer 122.This sample carrier 121 is molded components of being made by T shape, plate shape or mushroom-shaped plastics.This sample carrier can not be made of plastics yet, but can comprise biocompatible insertion material (for example semiconductor material).Sample carrier 121 comprises the sample receiver 123 and the carrier pin 124 of plate shape.The outer shape complementation of the interior shape of access portal 111 and carrier pin 124 is so that form press fit each other.Between the edge of sample receiver 123, form gap 125.This gap 125 has reduced the danger of cross pollution between the sample.In addition, they can simplify taking off of cold storage unit.Respective sample storer 122 is fixedlyed connected with carrier pin 124.
Cold sample 130 is arranged on the sample receiver 123, especially, and the form of 130 one-tenth freezing drops of this cold sample.This drop is a cell suspending liquid, perhaps also has reference sample, and the sample of culture medium, labeling dye solution or detection sample is for example arranged.Surveying sample is reference sample, and it contains can be to the material of the sensitive reaction of critical environments condition.As surveying sample, for example can adopt chemical compound to radioactive radiation or undesirable temperature rise sensitivity, the control of surveying sample can monitor storage medium in freezer from the storage situation.
Lid film 114 is arranged to cover cold sample 130, and this lid film 114 is used for preventing from heat eliminating medium or from the pollutant of environment.The common size of sample receiver 123 for example is 0.1 to 3mm.The gross thickness that stores matrix 100 for example is about 2mm.
For sample refrigeration of the present invention, store matrix 100 (not having lid film 114) and at first load cold sample and reference sample (when needing).This loading is for example undertaken by the droplet emitter, and this droplet emitter is for example described in the EP-B0804073.Be under the freezing state in storage matrix 100, sample is aimed at sample receiver 123 emissions as droplet, and when sample hit on this sample receiver 123, they were with freezing.Equally, be in cryogenic following time storing matrix 100, in sample data storer 122, carry out write (for example the firing) of first sample data.After matrix is loaded, under the corresponding freezing conditions of refrigerating system, carry out lid film 114 and apply and will store in the matrix insertion supporting member.
In Fig. 2, represented the taking-up of sample from store matrix 100.According to the present invention,, corresponding cold storage unit 120 carries out the sample taking-up by being separated with matrix 110.Separation cooperates with decompressor 150 by cutter sweep 140 to be carried out.This cutter sweep anxious instrument 141 that cuts of having time, the profile of the blade of this cutting tool 141 and sample receiver 123 adapts.Cutting tool for example can form the hollow tubule with sharpening termination.Decompressor 150 comprises drift 151, and by this drift 151, sample data storer 122 separates with remaining storage medium 112, and carrier pin 124 can be extruded from access portal 111.When needing, also provide cutting tool, be used to improve the crosscut of storage medium 112 at an end of drift 151.This cutting and decompressor 140,150 can carry out active or passive cooling, store matrix 100 maintenance predetermined temperatures so that make.
Fig. 2 has represented special benefits of the present invention.By cutter sweep 140, sample 130 takes out with cold storage unit 120, can not open other stored sample.After taking-up, sample 130 also links to each other with sample data storer 122.Sample can be transferred in other storage matrix and/or the measurement mechanism under refrigerated condition or under the rising temperature conditions.For example, can on sample data storer 122, replenish sample data (data accumulation) according to measurement result.
Fig. 3 to 7 has represented that the present invention stores the schematic plan view of matrix (for example according to Fig. 1).Store matrix 100 and form similar common CD, access portal 101 is particularly arranged at the center, be used for storage matrix is installed in cold storage plant and/or read-write system.In the present embodiment, the sample receiver 123 of sample carrier forms rectangle.Their common surface size is about 0.1 to 30mm 2 Sample receiver 123 is arranged in fan-shaped 102 in groups.When sample took out with corresponding cold storage unit, matrix 110 remained with idle access portal 111.
Fig. 4 has represented to have the alternate embodiment of circular sample receiver 123.In each sample receiver 123, store several mm 3The drop of volume.Every can include up to 10 5Individual cell.Therefore, on being the whole storage matrix of about 12cm, diameter can store up to 10 8Individual cell.
Fig. 5 has represented to have a kind of version of circular sample receiver 123, compares the diameter of this sample receiver 123 littler (for example 0.01 to 1mm) with Fig. 4.Therefore, will increase at the sum that stores the cold storage unit on the matrix 100.Variability increases along with the taking-up of sample.
Pedestal storer 113 shown in Fig. 1 selectively according in the storage medium really routing arrange.These are as shown in Fig. 6 (annular storage channel) and 7 (storage channel of radial layout).By pedestal storer 113, store matrix and carry out other subregion.
Fig. 8 analyses and observe a kind of version of having represented to store matrix 200, and this storage matrix 200 has matrix 210, and this matrix 210 is formed by the sample carrier 221 of cold storage unit.Sample carrier 221 has at the sample data storer 222 of a side and at the sample receiver 223 of opposite side.Sample carrier 221 is molded components of for example being made by plastics or semiconductor material, and wherein, sample receiver 223 forms recess.Sample carrier 221 is connected to each other by cut-off point.Sample data storer 222 forms one deck storage medium that is arranged in matrix 210 bottom sides.Provide lid film 214 at the upside that stores matrix, sample 230 is covered by this lid film 214.Lid film 214 surrounds matrix 210 on the outward flange of matrix 210, and have around projection 215.
Store the use of matrix 200, especially loading and data storing are carried out according to above-mentioned principle.In order to remove data, cold storage unit 220 separates (for example fracture, cut-out etc.) with carrier 221 and sample data storer 222 by proper tools from storing matrix 220.According to purposes, cut-off point 224 has been designed to prespecified geometric, as shown in Figure 9.
In Fig. 9, white line is represented the distribution of cut-off point 224.Especially, in each frame block zone, arranged sample carrier with sample receiver.Sample receiver has various geometric configuratioies in storing matrix 200, for example towards inside, they can compacter (left figure part) or narrower (right figure part).
The 3rd embodiment that has represented storage matrix 300 of the present invention among Figure 10.This storage matrix has the plate-shaped base body 310 of even plate shape.There are not joint or cut-off point in the present embodiment.In the present embodiment, store on the matrix 300 as long as sample 230 is arranged in, cold storage unit 320 just forms a unit.For sample carrier 321, provide the sample that is used for each sample accommodating layer.This sample accommodating layer comprises plastic material, and it has the minimum bonding strength (for example being made by PTFE or rubber) with matrix 310.Especially, in low temperature range, provide minimum bonding strength.
In order to separate sample 330, this sample separates (for example pull down, shoot off, push or draw back) with the sample accommodating layer from matrix by suitable tools.Sample data storer 322 is retained in the matrix bottom side.
In the present embodiment, sample 330 prevents to be polluted by covering 314.This lid 314 is formed by lid, and this lid seals against matrix 310 by lip ring 315.
In Figure 11, the skeleton view part on top has been represented according to the present invention the also storage matrix 400 of an embodiment.Store matrix by this, the form with pre-punching or press fit in matrix 410 provides cold storage unit 420.Matrix 410 and cold storage unit 420 form dull and stereotyped, are furnished with one deck storage medium 412 in its bottom side.This storage medium 412 (data carrier film) equally can pre-punching, and be arranged in the bottom side of matrix 410, and required flatness is arranged, so that light writes and sense data.
In the bottom side of Figure 11 figure part, represented cold storage unit 420 with the amplification form.Provide recess in top side matrix 410, that form sample carrier 421, as sample receiver 423.Cold sample (for example hanging drop) is arranged in this sample receiver.Sample 430 prevents to pollute by lid film 414.Also have, on lid film 414, can provide and the corresponding hole of the profile of cold storage unit 420.Usually, according to the present invention, lid or lid film also can form storage medium.Be similar to the instrument shown in Fig. 2 by utilization cold storage unit 420 is taken off from storing matrix 400, sample 430 can take off with sample carrier 420, sample data storer 422 and the lid film 414 that cuts.Store matrix 400 and be fixed on the supporting member, and separate with matrix 410 with cutter sweep 440 by drift 451 (blade is perhaps arranged when needed).Cutter sweep 440 provides movable ram 441, and at cold storage unit 420 after separatings, this movable ram 441 should extrude cutter sweep by cold storage unit 420.
Figure 12 by case representation a kind of version of single cold storage unit 420 of Figure 11 embodiment, this cold storage unit 420 has sample carrier 421 and sample receiver 423.For this version, lid 414 forms two membranes.Porous layer 415 covers sample carrier 421 as lid.Provide the sealant 416 with extension 417 on it, this extension extends upward from substrate plane.This extension 417 can manually or by suitable tools be drawn back from substrate plane.Like this, open the bottom side on sample carrier 20 415.This process can be carried out under the deep refrigeration situation, perhaps also can carry out under thawing condition.Liquid in sample receiver 423 can carry out quick exchange.For example, can be from the cold protective agent of cell suspending liquid flush away.
Lid 414 also can comprise data or the mark that is used to discern sample.According to version, another structure of lid 414 can form extra play.
The principle of in Figure 13, also having represented the multilayer lid by another embodiment of the present invention.Store matrix 500 and comprise matrix 510, this matrix 510 has mushroom-shaped projection 511, and sample carrier 521 places on this mushroom-shaped projection 511.Sample carrier 521 is molded components, has at the sample receiver 523 of upside with at the fixedly recess 524 of bottom side.Fixedly recess 524 and projection 511 resemble together and work the button, as releasable mechanical fastener.Be positioned at the opposite side of sample carrier 521 as the data carrier layer of storage medium 512, this data carrier layer forms sample data storer 522, and this sample data storer 522 links to each other with corresponding sample carrier 521.The double-deck principle that lid 514 adopts as shown in figure 12.
In order when storage matrix 500 is in freezing state, to take off sample carrier 521, below sample carrier 521, thrust plane or wedge tool.By this instrument, make respective bump 511 and fixedly the connection between the recess 524 unclamp.Therefore, the part of sample and sample carrier 521 and lid 514 is separated with storage matrix 500 together.Also for this embodiment, when separating, the connection of sample data storer 522 will lose.But sample data also can be provided in the suitable part of lid 514.
Represented that at the embodiment shown in Figure 14 to 26 storage matrix 600 forms by at least one wiring board 610, this wiring board 610 is corresponding to matrix, and one or single cold storage unit 620 resemble and be arranged on this wiring board the circuit (chip).Wiring board 610 supporting electrical connector 611 (conductive path) or light web members (light transmitting fiber), this electrical connector or light web member link to each other with receiver mount 612 respectively, and this receiver mount 612 is used for receiving cold storage unit by external control device (not shown).This receiver mount is equivalent to the socket of circuit common fabricated section substantially, and (for example Figure 15) carried out in the contact of cold storage unit in this fabricated section.On receiver mount 612, can provide extension wire, be used to carry out signal modulation, conversion of signals or detection data-signal from connecting line 611 or light-path.
Connecting line 611 can be in the top side of the wiring board 610 with receiver mount 612 (the last figure part of Figure 14), perhaps in opposite side (figure below part of Figure 14).Under latter event, receiver mount 612 is close arrangement more.Figure below part of Figure 14 has also represented to be used for the counting circuit 613 of cold storage unit control on wiring board 610, required RAM storer can be provided simultaneously when needed.
Each receiver mount 612 is used to receive cold storage unit 620.Each cold storage unit 620 comprises sample carrier 621, and is similar with above-mentioned functions, and this sample carrier 621 links to each other with sample data storer 622.According to particular preferred embodiment of the present invention, cold storage unit is formed by same known integrated circuit (for example reservoir part).This circuit comprises at least one the RAM storer as sample data storer 622.This cold storage unit 620 also can comprise complete counting circuit, can realize the function of cold storage unit by this counting circuit, and cold storage unit can be by this counting circuit and and external communications.Preferably, sample carrier 621 is formed in the vinyl cover or encapsulation of integrated circuit, or links to each other with them.
For example, sample receiver 623 is the recesses in plastic cover, as shown in figure 15.Common chip is of a size of 7 * 14mm, and it is the lower surface of 1mm that sample receiver 423 can have the about 4 * 10mm and the degree of depth.By these measures, in cold storage unit 620, can hold up to 500 ten thousand cells.
Can provide the additional control device that is used to operate sample sensor and/or display unit 624 in the bottom of sample receiver 623.When needing, this control device comprises cooling and heating element, for example Peltier element, stratie, and they are used to control the cooling or the heating of sample, perhaps control has the cooling or the heating of the material that increases thermal capacitance, so that reduce the heat load of sample in the chip transportation process.As display device, light source can be provided, this light source for example sends signal to the predetermined state of cold storage unit or sample, and perhaps this light source is used for the measurement to sample 630 as measurement light source.In addition, cold storage unit 620 has lid 614, and this lid protection sample is avoided polluting, evaporated and distillation.Lid 614 is plastic caps, the film of for example burn-oning, and perhaps other layer shape parts, it seals with releasable with sample carrier 621 and is connected.
Sample carrier 621 also is used as the guiding piece of the contact-connection assembly for electric 625 of cold storage unit.Particularly, this contact-connection assembly for electric links to each other with sample data storer 622, and links to each other with display device 624 with control when needing.
With opposite by the known diagnosing chip of cellular biological technique, for cold storage unit 620, be not connected between sample 630 and sample data storer 622, control and/or display device 624, this control and/or display device 624 are used for detecting the electrical quantity at the freezing cell of sample.
The lid 614 of Figure 15 also can be replaced by the cold containers 615 of Figure 16.By this cold containers 615, the top side of sample carrier 621 is carried out sealing screw with cylindrical container body 617 and is connected.This cold containers 615 comprises anti-cold moulding material material.The advantage of the embodiment of the invention of representing among Figure 16 is that cold containers 615 also can artificial loading, for example passes through suction pipe.
Figure 17 to 26 has represented other specific embodiment of cold storage unit 620 of the present invention.The cold storage unit 620 of Figure 17 comprises sample carrier 621 and sample data storer 622.This sample data storer 622 constitutes similar known electronic storage chip with contact electrode 625 and encapsulation 626, wherein is furnished with storage circuit, also has counting circuit when needing.Encapsulation 626 comprises common plastic material.
Sample carrier 621 is installed in the top side of encapsulation 626, perhaps as a part that encapsulates 626.Sample carrier 621 comprises plastic frame 627, in this plastic frame 627, in order to receive sample, is combined with at least one cold containers 615.This plastic frame 627 is injection molded, its size for example with the encapsulation 626 surperficial corresponding.It is porose that side frame partly provides, and cold containers 615 is arranged in this hole.
Each cold containers 615 forms at least one elongated sample chamber.At least one sample chamber is an elongated shape, and like this, internal cross section is far smaller than its length.For the sample chamber, for example can provide flexible pipe, hollow needle, tubule etc.The internal diameter of sample chamber for example is in the scope of 5 μ m to 4mm.Length can be selected in 0.5cm to 10cm scope.The cross-sectional diameter of sample chamber and the ratio of length are preferably less than 1/10.At least one becomes the cold containers 615 of pipe or flexible pipe shape to be arranged to have to be beneficial to quick loading or turned letter sample chamber, has very high capable of miniaturization, and very high chilling rate is arranged.
For in the embodiment of the invention shown in Figure 17, first cold containers 615 is formed by the crooked shape flexible pipe (part expression) that is arranged in the framework 627.Cold containers 615 being loaded back (seeing arrow) by flexible pipe, cut the flexible pipe part that is illustrated by the broken lines, like this, stay the part of drawing as independent cold containers (for example 616).All cold containers 615 have identical sample 630 as a unit load.This helps segmenting the sample part.For medical tripping device 400, sample part 616 can be separated with cold storage unit 620 with freezing or thawed state, can not influence remaining sample part simultaneously.
Can provide additional control device and/or display unit 624 on the surface of encapsulation 626 and/or on the framework 627 at sample receiver 623, this control device is used to operate sample and/or sensor.When needing, this control device comprises cooling and heating element, for example Peltier element, stratie etc.They are used to control the cooling or the heating of sample, and perhaps control has the cooling and the heating of the material that increases thermal capacitance, so that reduce for example heat load in the chip transportation process of sample.Sensor and/or display can have light source, and this light source for example sends signal to the predetermined state of cold storage unit 620 or sample, and perhaps this light source is used for the measurement to sample 630 as measurement light source.
In addition, each end of cold containers 615 can provide lid 614, and this lid protection sample is avoided polluting, evaporated and distillation.Film that lid 614 for example is plastic cap, burn-on or parts in addition, the termination of it and corresponding cold containers is connected and sealed.When flexible pipe during as cold containers, this lid also can be formed by the part of this flexible pipe self, and this flexible pipe is clipped together in its termination.
According to Figure 17, also can replace passing and cut flexible pipe when needed, but can provide a plurality of tubular cold containers of making by rigid material 615 as sample receiver 623, these sample receivers 623 are arranged to longitudinal direction vertical (Figure 17) or parallel (Figure 18) with cold storage unit 620.For example, for the embodiment of Figure 18, five cold containers 615 can be combined in the encapsulation 626 (inclosure).This can realize by cold containers 615 is injected in the encapsulating material, or realize by bonding agent is bonding.Cold containers 615 is formed by hollow needle or tubule.
When cold containers 615 is loaded, make an end of this cold containers 615 that low pressure be arranged, and receive cold sample by relative entrance point 617.Also can not provide low pressure, but sample receiver can provide capillary force in cold containers 615.Particularly, for the embodiment of Figure 18, identical or different cold sample 631,632 ... can pack in each cold containers 615.Cold containers 615 preferably is spaced apart from each other, and like this, supply side 617 is arranged to miniature or minimum titer plate form.
According to the optional embodiment of the cold storage unit 620 of the present invention shown in Figure 19, the cold containers of sample carrier 622 forms flexible pipe, and the diameter of this flexible pipe is variable along its longitudinal direction.Part 618 has than minor diameter, and in chamber portion 619, this flexible pipe is widened greatly.Cold containers 615 comprises a plurality of chamber portions 619, and this chamber portion can advantageously separate with cold storage unit by mechanical separation device 400.Cold containers is installed in the encapsulation 626 of sample memory 622 (for example bonding or local injection).The loading of cold containers 615 can carry out under the situation that forms low pressure, by this low pressure, can absorb the cold sample that suspends from the entrance point 617 of cold containers 615.
According to Figure 20, cold containers 615 also can be formed by flexible pipe, and it has only a chamber portion 619, and as shown in the figure, this cold containers loads by flexible pipe part 618 or turns, and perhaps also can select partly to load or turn by a plurality of flexible pipes.The chamber portion 619 of Figure 20 is formed by membrane material, and it is bonded in the encapsulation 626.
With opposite by the known diagnosing chip of cellular biological technique, for cold storage unit 620, do not connect between sample 630 and sample data storer 622 and/or control, sensor and/or display device 624, this display device 624 has been represented the scheduled electrical parameter of the frozen cell in sample.
In Figure 21 and 22, the loading of further having represented sample in detail is with the taking-up from cold storage unit 620.According to Figure 21, load and for example to be undertaken by loading attachment, this loading attachment has in a plurality of sample reservoir 710 of a side with at the pressure apparatus of opposite side.Cold storage unit 620 comprises frame shape sample carrier 621, with embodiment illustrated in fig. 17 similar, is furnished with into a plurality of cold containers 615 of tubule or flexible pipe shape on this sample carrier 621, and the supply side 617 of these cold containers 615 stretches in the sample reservoir 710.This sample reservoir 710 is accumulator tanks, after extracting sample sample is placed this accumulator tank.Pressure apparatus 720 comprises pressure annex 721 and connecting line 722, and this pressure annex 721 can be arranged on the opposite end of cold containers 615 in pressure-tight mode, and by this connecting line 722, and all cold containers 615 can add and are pressed into low pressure.Preferably, the termination of cold containers 615 is mounted for public receiving element on frame part, pressure annex 721.For example, they can be opened in the surface of framework 627.Under the low pressure effect, sample 630 is packed in the cold containers 615.
After sample carrier 621 loaded, cold storage unit 620 separated with loading attachment.When needing, input end 617 is shortened on the framework 627.Cold storage unit 620 is arranged in and stores on the matrix 610 (seeing Figure 14), and transfers in the environment with lower temperature with this storage matrix 610, for example in the cold containers in the freezer.
In Figure 22, represented a kind of feasible method that sample is taken out from the cold storage unit 620 with crooked shape cold containers 615.Sample part 616 is separated by mechanical separation device 400, and this mechanical separation device 400 is cutter sweep for example.This can be under the lower temperature state favourable carrying out, so all the other samples can remain unchanged.
In Figure 23 to 26, represented to adopt the embodiment of the invention of cold storage unit 620, opposite with the foregoing description of sample retainer 621, this cold storage unit 620 is not combined in the encapsulation of storage circuit (storage circuit), but in its host material.For example, Figure 23 has represented the part (not expression encapsulation and contact-connection assembly for electric) of cold storage unit 620.Among the figure to analyse and observe the storage circuit 800 that form has represented to have matrix 810 and integrated component 820.This matrix for example is semiconductor wafer, is used to make the identical of integrated circuit with common.At the upside of matrix 810, parts 820 are handled by the known semiconductor technology.In the bottom side of matrix 810, channel shaped sample chamber 623 forms sample receiver, and this sample receiver is by 820 sealing of lid layer.The measurement size of sample chamber 623 is 400 μ m (for example cross sectional dimensions) and 20mm (length).Sample chamber 623 also can be formed in the matrix structure layer that is arranged on the matrix (seeing Figure 24).Lid layer 830 comprises plastic material, glass or semiconductor material.
In addition, sample chamber 623 can be provided, as shown in figure 24 in a plurality of planes.In this structure 810, can provide the first matrix structure layer 811 and the first lid layer 830 with sample chamber 623.On the first lid layer 830, can provide another matrix structure layer 812 and another lid layer 831 at least with sample chamber 623.By this embodiment, preferably on corresponding sample data storer, can absorb than the large sample volume.According to Figure 23 and 24, dry load or sample are undertaken by hose connector on cold storage unit 620, and this hose connector is combined in the encapsulation of sample data carrier 622, and cut off or pinch off after use.
In Figure 25 and 26, the various geometric configuratioies of the channel shaped sample receiver 623 in matrix 810 have been schematically illustrated.For example, can provide bending or U-lag road shape with various sectional dimensions, when needs are, they can be arranged to nested each other.
The embodiment of the invention shown in Figure 14 to 26 has series of advantages.Cold storage unit is formed by electronic chip, but this electronic chip comprises the electronic memory of exterior read-write, as the sample data storer.Therefore do not need to rely on thermoregulator read/write head, in the CD storer.In chip, be furnished with at least one and the corresponding sample receiver of one or more sample.This chip and/or receiver mount can have electronic switch, are used to control additional function element, sensor and/or warning system.Structure shown in Figure 14 can form three-dimensional multilevel cold matrix, and wherein, a plurality of wiring boards 610 are stacked into one on another with a plurality of cold storage units.
Chip-shaped storage unit can take off from wiring board with freezing state without a doubt, and transfers on the other wiring board, measurement mechanism for the treatment of stations, can not lose sample data simultaneously.But cold storage unit external electrical addressing.
In addition, for the maltilevel security measure, but cold storage unit can provide one or more signs, can read automatically or the colour-coded of vision control.According to Figure 15, to compare with the size of common integrated circuit, this cold storage unit can also minimize.By minimizing, preferably can carry out Optimal Control, electrically contact with replacement.
At least one wiring board that stores matrix can link to each other with the computing machine bus-bar system, and by this computing machine bus-bar system, each cold storage unit can be inquired about separately and control.Cold storage unit shown in Figure 15 can be according to purposes and variation (for example circle or polygon sample carrier).
Key character of the present invention will be concentrated in the following description.
Storage substrate combination of the present invention the data sink of material receiver and specific sample.In the low-temperature storage process, can optionally take out material (cell, cell suspending liquid) and read/storage data and/or data material.
The multiple data identification that guaranteed, wherein, sample and sample data arrangements of memory are in same matrix position or next-door neighbour's substrate location.In addition, storing matrix can dye, and like this, based on the color of cold storage unit and matrix, can judge which each sample partly store matrix from.
Cold storage unit can sterilize and reuse at an easy rate.And they are formed with the protective device of sample, are subjected to the influence of the environmental baseline of the present invention's refrigeration to avoid this sample.
Can also make the matrix and the cold storage unit that store matrix form a unit with colour or numeral or simulation sign sample, this makes two parts that clearly structure be arranged at any time.This helps automatically, optics control (for example dyeing and code detection).
At first, sample data can be stored on the cold storer of the present invention in the scope of megabyte in kilobyte.This is particularly conducive to the storage measurement result.
In the expectation process in serviceable life that stores matrix, may at any time carry out data and replenish (data accumulation).Like this, all data of sample and operation that all carry out, measurement, processing etc. can not have in the file that interruptedly is recorded in specific sample fully.
Especially, in chip shape storage unit, the particular procedure of sample can optionally be undertaken by preset program and store.For example, in the refrigeration framework, the heating that can be scheduled to, cooling, measurement, control and warning/display routine, and can in program data memory, carry out record.At freezing state, different temperatures can be used for different cold storage units with process of measurement.For example, can cause the part and thaw, so that carry out sample measurement.Above-mentioned heating element can be used for all embodiment that the present invention stores matrix, so that the spot heating storage medium.On storage medium, can carry out spot heating, make respective sample simultaneously Keep cool state.
According to the present invention, store matrix can with electronic databank's combination operation, in this electronic databank, stored the sample data of matrix in the mirror image mode.
The lid of sample receiver can partially transparent or transparent fully.By this layer, can be in conjunction with optics and other measuring method in sample receiver.For example, sample can be represented with illustration.Also can carry out fluorescence measurement, dielectric medium measurement and/or ultrasound wave represents.
Freezer of the present invention comprises a plurality of above-mentioned storage matrix, control device and treating apparatus, and this treating apparatus is used for operation and stores matrix and be used to take out sample.
Importantly, can in various embodiment of the present invention, implement separately and the enforcement of appropriate combination ground in the feature of the present invention described in above stated specification, claim and the accompanying drawing.

Claims (19)

1. method that is used to refrigerate, described method comprises:
Storing a plurality of samples of layout on the matrix;
The sample data of representing the feature of a corresponding sample is stored in the ad-hoc location that stores on the matrix, wherein, corresponding sample arrangement is on sample carrier, relevant sample data is stored in the sample data storer, the contact of sample data storer and sample carrier is unique, sample data can clearly be got in touch with respective sample by their storage location, and, sample carrier and sample data storer form one and can discharge so that take out the global facility of sample from storing matrix, and wherein integrated circuit is as the sample data storer.
2. method according to claim 1, wherein: sample data be stored near the of respective sample or below.
3. method according to claim 1 and 2, wherein: the identification information of sample, store as sample data about information, measurement result and/or the treatment step of the material property of sample.
4. method according to claim 1 and 2, wherein: sample data is read when storage matrix is in freezing state and/or is write.
5. method according to claim 1, wherein: sample takes off from storing matrix with the sample data of storage, and transfers on the other storage matrix or transfer on measurement mechanism or the treating apparatus.
6. method according to claim 1 and 2, wherein: sample data stores by light, magnetic, topology or electromagnetism.
7. method according to claim 1 and 2, wherein: sample comprises the suspending liquid of at least one cell, cellular component, cell aggregate and/or tissue.
8. method according to claim 7, wherein: sample comprises additional reference and surveys sample.
9. method according to claim 1 and 2, wherein: freezing, heat or the sample that thaws stores under the situation that matrix are in freezing state at all the other and measures and/or handle, measurement result stores as sample data.
10. method according to claim 1 and 2, wherein: control at least one sample at the state that stores on the matrix by the counting circuit that links to each other with sample.
11. a storage matrix that is used to refrigerate a plurality of samples, this storage matrix comprises:
A plurality of cold storage units, these cold storage units are respectively by being used to receive the sample carrier of sample and the combiner of sample data storer forms, the sample data of representing the feature of a corresponding sample is stored in the ad-hoc location that stores on the matrix, wherein, corresponding sample arrangement is on sample carrier, relevant sample data is stored in the sample data storer, the contact of sample data storer and sample carrier is unique, sample data can clearly be got in touch with respective sample by their storage location, and, sample carrier and sample data storer form one and can discharge so that take out the global facility of sample from storing matrix, and wherein integrated circuit is as the sample data storer.
12. storage matrix according to claim 11, wherein: each cold storage unit is arranged in the matrix that stores matrix releasedly.
13. according to claim 11 or 12 described storage matrix, wherein: a moulding part is as cold storage unit.
14. storage matrix according to claim 11, wherein: this sample carrier is combined in the structure of integrated circuit.
15. storage matrix according to claim 14, wherein: this sample carrier has cold containers.
16. storage matrix according to claim 14, wherein: this sample carrier has at least one blown tubular, tubule shape or channel shaped sample chamber.
17. storage matrix according to claim 14, wherein: this sample carrier is as the channel shaped sample receiver in the matrix of integrated circuit.
18. storage matrix according to claim 14, wherein: cold storage unit comprises counting circuit, controls the function of cold storage unit by this counting circuit, and makes cold storage unit and external communications by this counting circuit.
19. a cold storage unit comprises:
The sample carrier that is used for sample; And
Integrated circuit, it is as the sample data storer, wherein, corresponding sample arrangement is on sample carrier, relevant sample data is stored in the sample data storer, the contact of sample data storer and sample carrier is unique, and sample data can clearly be got in touch with respective sample by their storage location, and sample carrier and sample data storer form global facility each other.
CN018201458A 2000-12-07 2001-12-07 Cryostorage method and device Expired - Fee Related CN1585894B (en)

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DE2000160889 DE10060889A1 (en) 2000-12-07 2000-12-07 Cryopreservation method for cells and cell components comprises applying samples to e.g. a CD as a storage substrate and burning position-specific data on to disk.
DE10060889.2 2000-12-07
DE2001144925 DE10144925A1 (en) 2001-09-12 2001-09-12 Cryopreservation method for cells and cell components comprises applying samples to e.g. a CD as a storage substrate and burning position-specific data on to disk.
DE10144925.9 2001-09-12
PCT/EP2001/014400 WO2002046719A2 (en) 2000-12-07 2001-12-07 Cryostorage method and device

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US6931864B2 (en) 2005-08-23
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PT1340062E (en) 2013-01-25
EP1340062A2 (en) 2003-09-03
EP2302351A1 (en) 2011-03-30
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WO2002046719A3 (en) 2002-12-19
ES2397721T3 (en) 2013-03-11
EP2302351B1 (en) 2017-03-01
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WO2002046719A2 (en) 2002-06-13
DK1340062T3 (en) 2013-02-11

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